Antiretroviral Therapy and Metabolic Disorders

The introduction of HAART in recent years has significantly modified the course of HIV disease, prolonging survival and improving patients’ quality of life. However, early data have raised concern that HAART regimens, especially those including protease inhibitors (PIs), except atazanavir, are asso­ciated with an increased incidence of meta­bolic (hyperlipidemia, insulin resistance) and somatic (lipodystrophy/lipoatrophy) changes that in the general population are associated with an increased risk for cardio­vascular disease (coronary and peripheral artery disease and stroke), producing an intriguing clinical scenario [54].

HIV-associated lipodystrophy/lipoatrophy, first described in 1998 [55], is characterized by prominence of the dorsocervical fat pad (“buffalo hump”), increased abdominal girth and breast size, lipoatrophy of subcutaneous fat of the face, buttocks, and limbs, and prominence of the veins on the limbs [55]. The overall prevalence of at least one physi­cal abnormality is about 50% in otherwise healthy outpatients. The differences between these prevalence rates (which ranged from 18 to 83%) may also have been confounded by patient sex and age, the type and duration of antiretroviral therapy, and the lack of an objective and validated case definition. Metabolic features significantly associated with lipodystrophy include dyslipidemia (about 70% of patients), insulin resistance (elevated C-peptide and insulin), type 2 dia­betes mellitus (8-10% of the patients), lactic acidemia, and elevated hepatic transaminas­es (non-alcoholic steatohepatitis) [56]. These metabolic abnormalities are more profound in those with more severe physician-assessed lipodystrophy and are associated with an increased risk in cardiovascular events (about 1.4 cardiac events per 1,000 years of therapy according to the Framingham score) [56].

Fig.

A detailed description of HAART-associ- ated metabolic syndrome and coagulation disorders, and of HAART-associated coro­nary and peripheral artery disease and stroke is provided by J. Capeau, L. Drouet, F. Boccara, P. Mercie, and A. Moulignier in separate chapters in this volume.

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